Sirolimus therapy for congenital hyperinsulinism in an infant with a novel homozygous KCNJ11 mutation
-
Sophy Korula
,
Aaron Chapla
Abstract
Background:
Congenital hyperinsulinism results in refractory hypoglycemia. If a therapy with diazoxide has been unresponsive this has been treated by subtotal pancreatectomy in the past. This therapeutic option poses an increased risk of developing diabetes at a later stage. There have been a few case reports on the use of sirolimus in such situations in the recent past.
Case presentation:
Our patient was started on sirolimus very early, on day 29 of life and at the age of 14 months is doing well on sirolimus therapy. His growth and development have been good and he has not had any major complications so far. Genetic testing showed a novel KCNJ11 homozygous mutation on next generation sequencing and the parents were heterozygous carriers.
Conclusions:
We report the successful use of sirolimus in the management of diazoxide unresponsive congenital hyperinsulinism with diffuse pancreatic involvement. We believe this is the youngest patient to be initiated on sirolimus so far.
Acknowledgments
We acknowledge the guidance of Prof Khalid Hussain (Chief of Endocrinology Division, Department of Paediatric Medicine, Sidra Medical and Research Center, Doha) by email correspondence towards practical aspects of management of this patient on Sirolimus.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Senniappan S, Shanti B, James C, Hussain K. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis 2012;35:589–601.10.1007/s10545-011-9441-2Suche in Google Scholar PubMed
2. Stanescu DE, Hughes N, Kaplan B, Stanley CA, De León DD. Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab 2012;97:E2026–30.10.1210/jc.2012-1356Suche in Google Scholar PubMed PubMed Central
3. Beltrand J, Caquard M, Arnoux JB, Laborde K, Velho G, et al. Glucose metabolism in 105 children and adolescents after pancreatectomy for congenital hyperinsulinism. Diabetes Care 2012;35:198–203.10.2337/dc11-1296Suche in Google Scholar PubMed PubMed Central
4. Senniappan S, Alexandrescu S, Tatevian N, Shah P, Arya V, et al. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med 2014;370:1131–7.10.1056/NEJMoa1310967Suche in Google Scholar PubMed
5. Thomas NJ, Brooke AM, Besser GM. Long-term maintenance of normoglycaemia using everolimus in a patient with disseminated insulinoma and severe hypoglycaemia. Clin Endocrinol (Oxf) 2013;78:799–800.10.1111/cen.12059Suche in Google Scholar PubMed
6. Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med 2009;360:195–7.10.1056/NEJMc0806740Suche in Google Scholar PubMed
7. Alexandrescu S, Tatevian N, Olutoye O, Brown RE. Persistent hyperinsulinemic hypoglycemia of infancy: constitutive activation of the mTOR pathway with associated exocrine-islet transdifferentiation and therapeutic implications. Int J Clin Exp Pathol 2010;3:691–705.Suche in Google Scholar
8. Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell 2007;12:487–502.10.1016/j.devcel.2007.03.020Suche in Google Scholar PubMed
9. Amato LA, Quigley CA, Neville KA, Hameed S, Verge CF, et al. Sirolimus treatment of severe congenital hyperinsulinism. Int J Pediat Endocrinol 2015;2015(Suppl 1):P123.10.1186/1687-9856-2015-S1-P123Suche in Google Scholar
10. Ünal S, Gönülal D, Uçaktürk A, Bilgin BS, Flanagan SE, et al. A novel homozygous mutation in the KCNJ11 gene of a neonate with congenital hyperinsulinism and successful management with sirolimus. J Clin Res Pediatr Endocrinol 2016;8:478–81.10.4274/jcrpe.2773Suche in Google Scholar PubMed PubMed Central
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Growth and growth hormone: recent papers on efficacy and adverse effects of growth hormone and World Health Organisation growth standards
- Review
- Allergic and non-allergic skin reactions associated with growth hormone therapy: elucidation of causative agents
- Original Articles
- Adherence to growth hormone therapy in children and its potential barriers
- Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test
- Growth response to growth hormone treatment in patients with SHOX deficiency can be predicted by the Cologne prediction model
- WHO 2006 Child Growth Standards overestimate short stature and underestimate overweight in Japanese children
- Identifying depressive symptoms among diabetes type and the impact on hemoglobin A1c
- Insulin resistance and lung function in obese asthmatic pre-pubertal children
- Obesity is associated with vitamin D deficiency in Danish children and adolescents
- Daily sitting time associated with the risk of metabolic syndrome in Korean adolescents
- Molecular basis and clinical presentation of classic galactosemia in a Croatian population
- Clinical outcome in a series of pediatric patients with congenital generalized lipodystrophies treated with dietary therapy
- Letter to the Editor
- Spondyloepiphyseal or spondylometaphyseal dysplasia in ancient Greek art
- Case Reports
- Sirolimus therapy for congenital hyperinsulinism in an infant with a novel homozygous KCNJ11 mutation
- Veganism as a cause of iodine deficient hypothyroidism
- A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty
- Addison’s disease presenting with perimyocarditis
Artikel in diesem Heft
- Frontmatter
- Editorial
- Growth and growth hormone: recent papers on efficacy and adverse effects of growth hormone and World Health Organisation growth standards
- Review
- Allergic and non-allergic skin reactions associated with growth hormone therapy: elucidation of causative agents
- Original Articles
- Adherence to growth hormone therapy in children and its potential barriers
- Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test
- Growth response to growth hormone treatment in patients with SHOX deficiency can be predicted by the Cologne prediction model
- WHO 2006 Child Growth Standards overestimate short stature and underestimate overweight in Japanese children
- Identifying depressive symptoms among diabetes type and the impact on hemoglobin A1c
- Insulin resistance and lung function in obese asthmatic pre-pubertal children
- Obesity is associated with vitamin D deficiency in Danish children and adolescents
- Daily sitting time associated with the risk of metabolic syndrome in Korean adolescents
- Molecular basis and clinical presentation of classic galactosemia in a Croatian population
- Clinical outcome in a series of pediatric patients with congenital generalized lipodystrophies treated with dietary therapy
- Letter to the Editor
- Spondyloepiphyseal or spondylometaphyseal dysplasia in ancient Greek art
- Case Reports
- Sirolimus therapy for congenital hyperinsulinism in an infant with a novel homozygous KCNJ11 mutation
- Veganism as a cause of iodine deficient hypothyroidism
- A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty
- Addison’s disease presenting with perimyocarditis
